These studies are intended to elucidate the hormonal regulation of hepatic free fatty acid metabolism and of de novo fatty acid synthesis, as studied in the isolated rat hepatocyte. The roles of insulin and glucagon are of particular interest, both with regard to a description of their effects on substrate metabolism and on several key lipogenic enzymes involved in both free fatty acid metabolism and fatty acid synthesis. Studies to date have strengthened the concept of hormonal regulation of these processes in various nutritional and disease states as an important determinant of hepatic lipid synthesis. The isolated rat hepatocyte has provided an excellent model for the study of these regulatory influences.